Two sample recovery devices are disclosed which are used for agitating solvents in inlet components of impactors receiving particulate matter from inhalers to recover particles of interest clinging to walls of such components. The sample recovery devices are designed to assist laboratory personnel in the measurement of the size distribution of particulate matter emitted from metered-dose, dry-powder, and similar inhalers. Such inhalers are in common use for the treatment of asthma today and are increasingly important in the therapeutic delivery of pharmaceutical products of biotechnology.
Inhalers must be tested regularly both during laboratory development of new products and for quality control and assurance for commercially sold products. The testing includes the measurement of the size distribution of particles emitted by the inhalers. The United States Pharmacopeia (USP) and similar British, European, and Japanese regulatory documents describe the use of cascade impaction devices as the acceptable method for measuring size distribution. Further, these international compendia describe the inlet that must be used to introduce the particles into the cascade impactor. This inlet is known commonly as the USP Induction Port and is shown on page 1902 of USP 24, Section 601.
Because particulate matter accumulates in this induction port during each test of an inhaler device, the laboratory analyst doing the testing must quantify the mass of active drug material deposited in the induction port. Typically, this procedure involves washing the inside walls of the induction port with a solvent known to dissolve the active drug ingredient and in some manner insuring that all drug material is recovered from the inside walls of the induction port. The wash solvent is then analyzed, typically by high-performance liquid chromatography (HPLC), to quantify the drug material.
The procedure of removing the drug material from the walls of the induction port is typically an ad hoc one with no assurance that all material is recovered. Further, the complete washing of the walls can consume a minimum of 50 ml of solvent and up to 200 ml of solvent. Consequently, the active drug compound is diluted with solvent, and the analysis via HPLC is relatively insensitive to the presence of the drug material, compromising the accuracy of the overall test.
In addition, pre-separators are used in many impactors. Dry-powder inhalers typically contain large diluent particles along with the active drug material. These diluent particles would interfere with the functioning of the cascade impactor designed to recover the dry particles allowed to enter the impactor during a test. Consequently, when an analyst tests a DPI, a pre-separator is attached to the inlet of the cascade impactor. Some drug material accumulates in this pre-separator during testing, and the active drug material captured in the pre-separator must be quantified. This procedure requires washing with a known amount of solvent, typically 50 ml to 200 ml in prior art procedures, and/or shaking the device.
The present invention relates to sample recovery or mixing devices that allow a user to add a minimum amount of solvent to parts that have recesses and bends, and to mix the solvent, while unattended, with active drug material that has been clinging to the walls. This will thoroughly wash the walls, and cause the active drug material to be dissolved in the solvent. The handling of the solvent to recover the material of interest after this washing process is according to standards.
The sample recovery devices of the present invention include fixtures that will hold the induction port, on the one hand, and a pre-separator on the other, and will rotate these components with the solvent contained in the chambers or passageways, after capping or sealing the openings, so the solvent acts on the material clinging to the interior surfaces.
The mixing devices insure that all of the surface areas are contacted by the solvent during the mixing process, so that it is known that all of the active drug material has been dissolved and is available for analysis.
The mixing devices are made so that they will permit use of a minimum amount of the solvent, and will yet provide adequate mixing to insure that all of the active drug materials are released.